Merck’s efforts to make headway in a cancer type that was an elusive target for its superstar oncology med Keytruda prove to be fruitful, as demonstrated through its Keynote-B96 trial in ovarian cancer.
The latest data drop is a more detailed look at a win from previously reported positive analyses of the phase 3 study, which tested Keytruda plus chemotherapy with or without Roche’s Avastin in patients with platinum-resistant recurrent ovarian cancer who have tried one or two prior lines of therapy, including at least one platinum-based chemotherapy.
In May, Merck revealed that the Keytruda regimen showed statistically significant and clinically meaningful improvements in progression-free survival (PFS), regardless of patients’ PD-L1 status. The therapy also met its secondary endpoint of overall survival (OS) in patients whose tumors express PD-L1, making it the first immune checkpoint inhibitor-based regimen to prove survival benefits in ovarian cancer.
Now, Merck is zooming in a little closer into the PFS gains and the OS win in a presidential symposium presentation at the 2025 European Society for Medical Oncology Congress in Berlin.
At an interim analysis with an April 2024 data cutoff, the Keytruda regimen had helped patients live a median of 8.3 months without their disease getting worse, compared to 6.4 months in the placebo arm. That translated into a 30% reduction in the risk of progression or death. The benefit was shared in patients who got or didn't receive bevacizumab, with 28% and 30% reductions, respectively.
Contrary to historical data in other tumor types, the Keytruda regimen's benefit was somehow more pronounced in the PD-L1-negative group. There, Keytruda's PFS improvement reached 44%, according to a subgroup analysis. In patients with positive PD-L1 expression below 10, the effect size was 26%, while the number was the smallest, at 21%, in patients with PD-L1 expression of at least 10.
In the PD-L1-expressing population, the PFS improvement was 28%. Patients in that subgroup who got Keytruda experienced a median PFS of 8.3 months versus placebo’s 7.2 months, according to a presentation.
Looking at the PD-L1 group specifically for OS, 69.1% of treated patients were alive at 12 months, compared to 59.3% in the placebo arm, according to results reported from the second interim analysis of the Keynote-B96 trial with a March 2025 data cutoff. By 18 months, the survival rate had climbed to 51.5% for those taking the Keytruda regimen and 38.9% for those on placebo.
The Keytruda-based therapy ultimately helped patients in the subgroup live more than four months longer than those on placebo, with a median survival of 18.2 months versus 14 months in the control group, according to the second interim analysis. Those with PD-L1 expression who received Keytruda had a 24% lower risk of death than the placebo arm.
As Nicoletta Colombo, M.D., from the European Institute of Oncology in Milan said in her presentation of the Keynote-B96 results, the observed OS is “among the longest reported in any clinical trial” for the cancer type, proving a clinically meaningful benefit. The data supports the regimen as a “new standard of care,” she said.
Based on the Keynote-B96 results, the FDA has accepted Merck's application under priority review, with a decision set for Feb. 20, 2026. The results speak to Keytruda's ability to “really transform a variety of different malignancies,” Marjorie Green, M.D., Merck’s senior vice president of oncology clinical development, said in an interview with Fierce Pharma.
A tough target
Merck has long been taking cracks at the ovarian cancer area, but the tough-to-treat cancer has historically proven difficult for Keytruda and other PD-1 inhibitors.
The company previously tested Keytruda, along with chemotherapy and followed by maintenance therapy with Merck’s AstraZeneca-partnered PARP inhibitor Lynparza, as a first-line treatment for patients with BRCA non-mutated advanced epithelial ovarian cancer. Despite proving improvements in PFS, the Keytruda-Lynparza combo couldn’t meet its OS endpoint, leaving Merck “uncertain” about the role of Keytruda in the indication, the company said at the time.
Green declined to comment on Merck's regulatory plan for that Keylynk-001 regimen.
Keytruda isn't alone in its ovarian cancer challenges. GSK’s own PD-1/PARP combo regimen of Jemperli-Zejula was also no match for ovarian cancer, which is typically considered a “cold tumor” as it doesn’t trigger a strong immune response and is therefore less responsive to immunotherapies like checkpoint inhibitors.
But, judging by the outcomes coming out of Keynote-B96, it seems Merck may have found a way in through the recurrent, platinum-resistant subgroup. The company recently announced that the trial had resulted in a statistically significant and clinically meaningful improvement in OS across all patients, not just the PD-L1-positive group. That data were not included in Merck’s ESMO presentation but will be presented at an upcoming medical meeting, the company said.
Editor's note: The story has been updated with the correct trial code and information on the FDA's priority review of Merck's application.